清脂护肝方对大鼠非酒精性脂肪性肝炎的作用研究

Effects and mechanism of “Qingzhi Hugan Prescription” on nonalcoholic steatohepatitis of rats

目的 :观察清脂护肝方对非酒精性脂肪性肝炎(non-alcoholic steatohepatitis,NASH)大鼠肝功能、血清炎症因子以及肝组织中Src家族相关激酶(Hck、Lyn)和Src抑制的蛋白激酶C底物(Src-suppressed C kinase substrate,SSe CKS)表达的影响并探讨其机制。方法 :以高脂饲料制备NASH大鼠模型,将造模成功的大鼠再随机分为模型组、清脂护肝方组(低、中、高3个剂量组),每组10只。模型组和正常组以0.9%Na Cl溶液灌胃,清脂护肝方组予清脂护肝方药液灌胃6周。实验结束后检测大鼠肝功能、肝组织中Hck、Lyn和SSe CKS蛋白表达水平以及血清中白细胞介素-1(interleukin-1,IL-1)、白细胞介素6(interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)水平。结果 :清脂护肝方能改善NASH大鼠的肝功能;清脂护肝方可下调Hck和Lyn的表达而上调SSe CKS表达,可降低血清IL-1、IL-6水平,但不影响TNF-α水平。结论 :清脂护肝方能够改善NASH大鼠肝功能、降低炎症因子水平,其机制可能是通过调控Hck、Lyn、SSe CKS的表达从而减轻肝脏的炎症反应。

Objective: To study the effects and the mechanism of “Qingzhi Hugan Prescription” on liver function, serum inflammatory factors and expression levels of Src family related kinases(Hck, Lyn)/Src-suppressed C kinase substrate(SSeCKS) in nonalcoholic steatohepatitis(NASH) of rats. Methods:NASH model was established in SD rats with high-fat food. The model rats were randomly divided into model group , three“Qingzhi Hugan Prescription” groups with high , medium and low dose respectively. There are 10 rats in each group. The rats in“Qingzhi Hugan Prescription”groups were gavaged with decotions of different doses and the rats in model group and control group were gavaged with 0.9%NaCl solution for 6 weeks. After that the rats were killed and serum liver function were detected. Hck, Lyn and SSeCKS in the rat liver tissue were detected by immunohistochemistry. The levels of interleukin-1(IL-1), interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) were measured by enzyme-linked immunosorbent assay. Results:“Qingzhi Hugan Prescription” improved rat liver functions of NASH rats, downregulated expressions of Hck and Lyn and upregulated expressions of SSeCKS. “Qingzhi Hugan Prescription” decreased serum IL-1 and IL-6 level but had no effects on TNF-α. Conclusions:“Qingzhi Hugan Prescription” may improve liver function and decrease inflammatory factors in NASH rats and its mechanism is possibly through regulation of the expressions of Hck, Lyn and SSeCKS.